Dihydroxy terminated teroligomers from morpholine-2,5-diones


Oligodepsipeptides (ODPs) attract increasing attention as degradable materials in controlled drug delivery or as building blocks for nano-carriers. Their strong intermolecular interactions provide high stability. Tailoring the side groups of the amino acid repeating units to achieve a strong affinity to particular drugs allows a high drug-loading capacity. Here we describe synthesis and characterization of dihydroxy terminated teroligodepsipeptides (ter-ODPs) by ring-opening copolymerization (ROP) of three different morpholine-2,5-diones (MDs) in bulk in order to provide a set of teroligomers with structural variation for drug release or transfection. Ter-ODPs with equivalent co-monomer feed ratios were prepared as well as ter-ODPs, in which the co-monomer feed ratio was varied between 9 mol% and 78 mol%. Ter-ODPs were synthesized by ROP using 1,1,10,10-tetra-n-butyl-1,10-distanna-2,9,11,18-tetraoxa-5,6,14,15-tetrasulfur-cyclodecane (tin(IV) alkoxide) that was obtained by the reaction of dibutyl tin(II) oxide with 2-hydroxyethyl disulfide. The number average molecular weight (Mn) of ter-ODPs, determined by 1H NMR and gel permeation chromatography (GPC), ranged between 4000 g·mol−1 and 8600 g·mol−1. Co-monomer compositions in ter-ODPs could be controlled by changing the feed ratio of co-monomers as observed by 1H NMR spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The amount of remaining monomers as determined by 1H NMR could be kept below 1 wt%. Macrocycles as main sources of byproducts as determined from MALDI-TOF-MS measurements were significantly lower as compared to polymerization by Sn(Oct)2. Glass-transition temperature (Tg) of ter-ODPs ranged between 59 °C and 70 °C.
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